Attention-deficit hyperactivity disorder, or ADHD, has engendered a great deal of debate over the past several decades. ADHD is a psychiatric disorder that involves symptoms of inattention (e.g. being easily distracted, having difficulty focusing) or symptoms of hyperactivity (e.g. being fidgety or restless), or a combination of both types of symptoms. The controversy surrounding ADHD became a bit louder in the 1990s, when the number of children being prescribed stimulant drugs like methylphenidate (Ritalin) and amphetamine (e.g. Adderall) to treat the disorder increased dramatically.

Part of the debate has focused on the long-term safety of prescribing these stimulant medications to children. There has also been a significant amount of discussion, however, about the nature of the disorder itself. For example, some have argued that ADHD is not a true pathology, but instead indicative of normal behavior that is considered less appropriate in certain cultures. According to this "social construct" hypothesis, only in those cultures where things like orderly behavior are emphasized is ADHD regarded as a disorder. Others have suggested that ADHD is overdiagnosed, and that diagnosis accuracy is inherently inconsistent because the physician often is forced to rely on second-hand reports of a child's behavior to make a diagnosis. On the other side of the debate are those who assert that ADHD is a distinct condition characterized by a specific neuropathology.

While these disagreements about medication safety and how to classify ADHD continue, however, another debate has been going on, if perhaps more quietly, among neuroscientists--most of whom subscribe to the perspective that ADHD has a neurobiological etiology. That discussion has centered on the neural bases of ADHD, and on the question of how accurate the hypotheses we've been relying on to understand the disorder really are.

ADHD and the brain

The two most widely-used pharmaceutical treatments for ADHD are methylphenidate and amphetamine. Although their mechanism of action is slightly different, both drugs cause levels of dopamine and norepinephrine to increase in the synapse, allowing increased interaction between those neurotransmitters and the receptors they act upon. Based on the purported effectiveness of amphetamine and amphetamine-like drugs, and because of the high levels of dopamine activity in areas of the brain thought to be important for attention, early hypotheses about the cause of ADHD focused on the potential role of deficits in dopamine functioning. In other words, it was recognized that drugs that increased dopamine levels improved the symptoms of ADHD, and then (with the support of experimental evidence) it was deduced that low levels of dopamine function might be part of what was causing the problem to begin with.

For example, one popular hypotheses, referred to as the low arousal hypothesis, suggests that low baseline levels of dopamine lead to deficiencies in attention and other executive functions. This may cause an individual to have trouble paying attention and be less interested in stimuli that aren't overly exciting (like schoolwork). The person may compensate for this lack of interest (i.e. low arousal) by frequently looking for stimulation from other things in the environment, which may lead to hyperactivity.

Recent findings

A study published in 2013 may help to shed some light on what is really going on in the ADHD brain. In the study, del Campo and colleagues used neuroimaging to assess structural differences in the brains of ADHD patients and healthy controls, and then looked at functional differences in the brains of these two groups before and after taking methylphenidate.

When it came to dopamine function, however, the ADHD patients and healthy controls were about the same. The groups had similar levels of dopamine receptor availability and both displayed equivalent increases in dopamine levels after taking methylphenidate. The individuals with ADHD did display overall deficits in attention compared to the control group, but the lack of differences in dopamine activity would suggest dopamine functioning was not the primary explanation for these differences. Interestingly, methylphenidate improved performance in a sustained-attention task in a baseline-dependent manner in both groups, regardless of ADHD diagnosis.

When the researchers looked only at the individuals in both groups who performed most poorly on tasks of attention, however, they saw something interesting. Poor performers in both groups had lower levels of dopamine activity in the caudate, an area of the brain that has previously been implicated in attention. Methylphenidate raised caudate dopamine levels in the poor performers from both groups back to normal levels. Thus, methylphenidate acted to change dopamine levels in areas associated with attention, and this improved performance--but it wasn't an effect that was limited to patients with ADHD. Instead, methylphenidate improved performance in everyone, and it seemed to rectify dopamine imbalances that were seen in poor attention performers, whether they had ADHD or not.

What this means for dopamine and ADHD

The study conducted by del Campo and colleagues supports the hypothesis that dopaminergic mechanisms are involved in processes of attention. However, because potential dysregulation of dopaminergic attentional processes was seen in poor performers in both groups, it suggests that dopamine dysregulation may not be the primary cause of ADHD.

It should be noted that del Campo et al. did not examine differences in dopamine activity in all areas of the brain, including some areas important for attention like the frontal cortices. However, the lack of abnormalities in dopamine function in ADHD patients in other areas of the brain involved in attention makes a dopamine-centered hypothesis of ADHD seem a bit tenuous. And that, of course, leaves us with more questions than answers.

If a dopamine deficiency isn't the underlying cause of ADHD, then what is? Perhaps other neurotransmitter systems, like the noradrenergic system, are also heavily involved. But another possibility is that ADHD is a heterogeneous disorder, characterized by a number of different underlying mechanisms. Which mechanisms are most important may depend on the individual case.

With this in mind, maybe a spectrum approach is a better way to look at ADHD. According to this perspective, attention deficits can be found on a continuum that ranges from minor to more severe symptoms, and the presentation and causes may vary from case to case. As we discover that many mental disorders are much more complex than we initially assumed, it seems the appreciation of heterogeneity offered by a spectrum approach is often more in line with what we see in real practice.

Neuroscientifically Challenged

Neuroscientifically Challenged is a neuroscience learning resource. In addition to a blog that discusses science current events in a non-technical manner, you will also find a number of videos and articles that you can use to learn about basic principles of science and the brain.